A certain kind of platinum complexes are useful as anti-tumor agent, and some of them have already been put to clinical use. In particular, specific stereoisomers of dichloro(1,2-cyclohexanediamine)platinum(II) (hereinafter may be abbreviated as “Dach-Pt(chlorato)” in some cases) have been developed as analogs of cisplatin which has been clinically used of old as an anti-tumor agent, and great interest has been taken in them because of their anti-tumor activity superior to that of cisplatin. Dach-Pt(chlorato) did not come to be clinically used mainly because of its low water-solubility. Whereas, cis-[(1R2R)]-1,2-cyclohexanediamine-N,N′]oxalate(2-)-O,O-platinum(II) (this is also called oxaliplatin), one of various compounds of modified Dach-Pt(chlorato) in which two chlorato groups, that are leaving ligands in the molecule, are substituted with oxalato groups, are currently widely used for clinical therapy due to its good water-solubility and potent anti-tumor activity.
With the view to impart still improved properties, conjugates of Dach-Pt with, for example, oxidized dextran or carboxymethoxydextran which are obtained by substituting the chlorato groups of Dach-Pt(chlorato) with a polymer having carboxyl groups on its side chains (see Non-patent document 1; cited documents are collectively listed later) and conjugate of poly(ethylene glycol)-block-poly(glutamic acid) and Dach-Pt (see Non-patent document 2) have been also provided. In particular, the Non-patent document 2 discloses that the conjugate described therein forms a polymer micelle and is solubilized in an aqueous medium, and shows not only anti-tumor activity comparable to oxaliplatin but also high drug stability and prolonged, high tumor accumulation.
In the Non-patent document 1, the substitution of the chlorato groups of Dach-Pt(chlorato) with the polymer is carried out by treating the Dach-Pt(chlorato) with silver nitrate, removing the resulting silver chloride by filtration, converting the filtrate to corresponding diaquo-complex (occasionally abbreviated as Dach-Pt(hydroxo)) having improved water-solubility, by passing through anion-exchange resin, and reacting the complex with the polymer in water (see page 1088 of the document). In the Non-patent document 2, almost the same procedure is also carried out except that the silver chloride produced is removed by centrifugation (see the right column at page 226 of the document).